Omega-3 fatty acids attenuate constitutive and insulin-induced CD36 expression through a suppression of PPARα/γ activity in microvascular endothelial cells

Omega-3 fatty acids attenuate constitutive and insulin-induced CD36 expression through a suppression of PPARα/γ activity in microvascular endothelial cells
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DOI:
10.1160/th10-09-0574
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发表时间:
2011-09-01
影响因子:
6.7
通讯作者:
De Caterina, Raffaele
De Caterina, Raffaele
中科院分区:
医学2区
文献类型:
--
作者:
Madonna, Rosalinda;Salerni, Sara;De Caterina, Raffaele

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微血管功能障碍发生在胰岛素抵抗和/或高胰岛素血症。游离脂肪酸(FFA)和氧化低密度脂蛋白(OxLDL)摄取增加可能导致氧化应激和微血管功能障碍,CD36是PPARα/伽马调节的清道夫受体和长链FFA转运体。我们研究了胰岛素治疗前后人真皮微血管内皮细胞(HMVECs)、+/-不同类型脂肪酸(FA),包括棕榈酸、油酸、亚油酸、花生四烯酸、二十碳五烯酸(EPA)和二十二碳六烯酸(DHA)的CD36表达和CD36介导的oxLDL摄取。胰岛素(10(-8)和10(-7)M)时间依赖性地增加Dil-oxLDL摄取和CD36表面表达(分别增加30+/-13%,p=24小时暴露于50 mU M-DHA或EPA,但不包括其他FA),钝化这两种成分(分别增加23+/-3%和29+/-2%,p
Microvascular dysfunction occurs in insulin resistance and/or hyper-insulinaemia. Enhanced uptake of free fatty acids (FFA) and oxidised low-density lipoproteins (oxLDL) may lead to oxidative stress and microvascular dysfunction interacting with CD36, a PPAR alpha/gamma-regulated scavenger receptor and long-chain FFA transporter. We investigated CD36 expression and CD36-mediated oxLDL uptake before and after insulin treatment in human dermal microvascular endothelial cells (HMVECs), +/- different types of fatty acids (FA), including palmitic, oleic, linoleic, arachidonic, eicosapentaenoic (EPA), and docosahexaenoic (DHA) acids. Insulin (10(-8) and 10(-7) M) time-dependently increased Dil-oxLDL uptake and CD36 surface expression (by 30 +/- 13%, p= 24 hour exposure to 50 mu M DHA or EPA, but not other FA, blunted both the constitutive (by 23 +/- 3% and 29 +/- 2%, respectively, p